title: Transcription, not synthesis, of interleukin-1 and tumor necrosis factor by complement.
abstract: Stimulation of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF alpha) production was studied during in vitro hemodialysis (HD) of whole blood using cuprammonium (Cup) or polysulfone (PS) dialyzers. In the absence of LPS, circulation of whole blood for two hours through Cup or PS dialyzers was not sufficient to induce production of IL-1 beta or TNF alpha in peripheral blood mononuclear cells (PBMC) during subsequent 24 hour culture. However, compared to freshly isolated cells, post-HD PBMC were primed to produce more IL-1 beta and TNF alpha when subsequently stimulated with LPS. Despite the lack of spontaneous monokine synthesis after HD, we observed transcription of mRNA coding for IL-1 beta and TNF alpha after two hours of LPS-free HD. When compared to levels of mRNA induced by 5 ng/ml LPS (100%), Cup induced 27 +/- 6% whereas PS did not induce detectable transcription of IL-1 beta. In the case of TNF alpha mRNA, Cup induced 26 +/- 8% and PS 13 +/- 3%. Recombinant C5a induced mRNA for IL-1 beta in PBMC without detectable IL-1 beta protein synthesis. We conclude that transcription of mRNA for IL-1 beta and TNF alpha during HD is primarily caused by complement activation by Cup, but that LPS or other factors are required for translation of IL-1 beta and TNF alpha mRNA transcribed during HD.
authors.affiliation: Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: R
authors.initials: R
authors.lastname: Schindler
authors.forename: G
authors.initials: G
authors.lastname: Lonnemann
authors.forename: S
authors.initials: S
authors.lastname: Shaldon
authors.forename: K M
authors.initials: KM
authors.lastname: Koch
authors.forename: C A
authors.initials: CA
authors.lastname: Dinarello
mesh_terms: D015152:Blotting, Northern; D002482:Cellulose / Q000031:analogs & derivatives; D015936:Complement C5a / Q000235:genetics; D003165:Complement System Proteins / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000235:genetics*; D008567:Membranes, Artificial; D011108:Polymers; D006435:Renal Dialysis; D013450:Sulfones; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D007375:Interleukin-1; D008567:Membranes, Artificial; D011108:Polymers; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; C017662:polysulfone P 1700; D015936:Complement C5a; D002482:Cellulose; D003165:Complement System Proteins; C009865:cuprammonium cellulose